Shock Wave-Induced Damage and Poration in Eukaryotic Cell Membranes.

Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for a variety of drug delivery applications. However, the mechanisms involved in shock wave-mediated membrane permeabilization are still poorly understood. In this study, the effects on both the permeability and the ultrastructural features of two human cell lineages were investigated after the application of underwater shock waves in vitro. Scanning Electron Microscopy of cells derived from a human embryo kidney (HEK)-293 and Michigan Cancer Foundation (MCF)-7 cells, an immortalized culture derived from human breast adenocarcinoma, showed a small amount of microvilli (as compared to control cells), the presence of hole-like structures, and a decrease in cell size after shock wave exposure. Interestingly, these effects were accompanied by the permeabilization of acid and macromolecular dyes and gene transfection. Trypan blue exclusion assays indicated that cell membranes were porated during shock wave treatment but resealed after a few seconds. Deformations of the cell membrane lasted for at least 5 min, allowing their observation in fixed cells. For each cell line, different shock wave parameters were needed to achieve cell membrane poration. This difference was correlated to successful gene transfection by shock waves. Our results demonstrate, for the first time, that shock waves induce transient micro- and submicrosized deformations at the cell membrane, leading to cell transfection and cell survival. They also indicate that ultrastructural analyses of cell surfaces may constitute a useful way to match the use of shock waves to different cells and settings.

The crucial role of diverse animal models to investigate cochlear aging and hearing loss.

Age-related hearing loss affects a large and growing segment of the population, with profound impacts on quality of life. Age-related pathology of the cochlea-the mammalian hearing organ-underlies age-related hearing loss. Because investigating age-related changes in the cochlea in humans is challenging and often impossible, animal models are indispensable to investigate these mechanisms as well as the complex consequences of age-related hearing loss on the brain and behavior. In this review, we advocate for a comparative and interdisciplinary approach while also addressing the challenges of comparing age-related hearing loss across species with varying lifespans. We describe the experimental advantages and limitations as well as areas for future research in well-established models of age-related hearing loss, including mice, rats, gerbils, chinchillas, and birds. We also indicate the need to expand characterization of age-related hearing loss in other established animal models, especially guinea pigs, cats, and non-human primates, in which auditory function is well characterized but age-related cochlear pathology is understudied. Finally, we highlight the potential of emerging animal models for advancing our understanding of age-related hearing loss, including deer mice, with their notably extended lifespans and preserved hearing, naked mole rats, with their exceptional longevity and extensive vocal communications, as well as zebrafish, which offer genetic tractability and suitability for drug screening. Ultimately, a comparative and interdisciplinary approach in auditory research, combining insights from various animal models with human studies, is key to robust and reliable research outcomes that better advance our understanding and treatment of age-related hearing loss.